International Journal of Clinical Case Reports 2024, Vol.14, No.3, 167-177 http://medscipublisher.com/index.php/ijccr 171 CTLA-4 and PD-1/PD-L1, and resistance to apoptosis by expressing anti-apoptotic molecules (Bou-Dargham et al., 2018). Tumors can also impair antigen presentation and create an immunosuppressive tumor microenvironment, which further aids in immune evasion (Bou-Dargham et al., 2018; Elsas et al., 2020). The complexity of these mechanisms necessitates a deeper understanding to develop more effective immunotherapeutic strategies. 4.3 Adverse effects and toxicity The adverse effects and toxicity associated with immunotherapy are significant barriers to its widespread use in breast cancer treatment. Immune checkpoint inhibitors, for instance, can lead to immune-related adverse events (irAEs) that affect various organs and systems, causing conditions such as colitis, dermatitis, and endocrinopathies (Henriques et al., 2021). The severity of these side effects can limit the dosage and duration of treatment, thereby reducing its efficacy. Moreover, the management of these toxicities requires careful monitoring and may necessitate the use of immunosuppressive drugs, which can counteract the benefits of immunotherapy (Basu et al., 2019; Henriques et al., 2021). 4.4 Patient selection and biomarkers Identifying the right patients who are most likely to benefit from immunotherapy remains a critical challenge. Current biomarkers, such as PD-L1 expression, are not always reliable predictors of response, as not all PD-L1 positive patients respond to treatment, and some PD-L1 negative patients do (Bou-Dargham et al., 2018). Ende et al. (2023) have been investigated for their correlation with pCR rate (Figure 3). Despite the large number of studies investigating which biomarkers are associated with a pCR, no ideal marker has reached the robustness and confidence to become widely implemented in clinical practice. The heterogeneity in immune evasion mechanisms among breast cancer patients further complicates the selection process. There is a pressing need for more precise biomarkers that can accurately predict response to immunotherapy and guide treatment decisions (Bou-Dargham et al., 2018; Retecki et al., 2021). Figure 3 Schematic representation of putative predictive markers linked to pCR after NAC in TNBC patients (Adopted from Ende et al., 2023) 4.5 Resistance to immunotherapy Resistance to immunotherapy, both primary and acquired, is a major hurdle in the treatment of breast cancer. Primary resistance occurs when patients do not respond to immunotherapy from the outset, while acquired resistance develops after an initial period of response (Bai et al., 2020; Hanna and Balko, 2021). The mechanisms underlying resistance are multifaceted, involving tumor-intrinsic factors such as genetic mutations and
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